Researchers at the Case Western Reserve University School of Dental Medicine will use a $3.25 million grant from the National Institutes of Health (NIH) to better understand how HIV impacts the human body, from mouth lesions to oral cancer.
HIV is a virus that attacks the body’s immune system and interferes with its ability to fight infections. More than a third of HIV patients will develop some form of oral side effects, like mouth ulcers from immune systems and can greatly impact quality-of-life.
The five-year research project will center on a type of white blood cell called regulatory T-cells, otherwise known as “Tregs.” These cells help the immune system signal an appropriate response to fight off infection. But sometimes Treg cells can malfunction, resulting in too many or too few of them. That can trigger diseases, including mouth and throat issues and eventually lead to prolonged inflammation. The goal is to identify genetic, microbiome and metabolic biomarkers that cause these oral complications.
Pushpa Pandiyan, an associate professor of biological sciences at the School of Dental Medicine, is leading the research as principal investigator.
“We’re looking at the dysfunctionality of immune cells and how these cells are associated with inflammatory lesions in the mouths of HIV/AIDS patients,” explained Pandiyan. “We also know that HIV patients also have a higher prevalence of oral cancer, and we want to see if the metabolic genes in these immune cells are associated with increased rates of cancer.”
This grant will allow the researchers to build on a previous Case Western Reserve-led study published last fall in Nature Communications, which focused on individuals taking HIV antiretroviral drugs. The research looked at how to increase T-cell counts while reducing the number of cells that behave dysfunctionally and cause inflammation.
Pandiyan said the new NIH grant will support work designed to identify potential targets for therapeutics in HIV-positive patients and increase understanding of the gut microbiome’s role in oral manifestations of HIV.
“We’d like to eventually expand our current research to examine the role of bacteria found in the mouth and the gut microbiome,” Pandiyan said. “Good bacteria can be helpful while fighting disease, but it can shift in a way that results in unwanted inflammation. These changes in the microbiome affect the cytokines (a type of protein produced by immune and non-immune cells) in HIV patients and warrant further study.”
The research team will involve faculty from the Case Western Reserve School of Medicine, including: Adam Burgener, Mark Cameron, Mahmoud Ghannoum and Jeffrey Jacobson.
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